- 作者：Kenneth Chan ; MPharm? ; Riyaz S. Patel ; MD? ; &dagger ; ; &Dagger ; ; Paul Newcombe ; PhD§ ; ; Christopher P. Nelson ; PhD¡Î ; Atif Qasim ; MD¶ ; ; Stephen E. Epstein ; MD# ; Susan Burnett ; PhD# ; Viola L. Vaccarino ; MD ; PhD?? ; A. Maziar Zafari ; MD ; PhD?? ; Svati H. Shah ; MD&dagger ; &dagger ; ; Jeffrey L. Anderson ; MD&Dagger ; &Dagger ; ; John F. Carlquist ; PhD&Dagger ; &Dagger ; ; Jaana Hartiala ; MS&dagger ; &dagger ; ; Hooman Allayee ; PhD&dagger ; &dagger ; ; Kunihiko Hinohara ; PhD¡Î¡Î ; Bok-Soo Lee ; PhD¶ ; ¶ ; ; Anna Erl ; MD## ; Katrina L. Ellis ; PhD??? ; Anuj Goel ; PhD&dagger ; &dagger ; &dagger ; ; Arne S. Schaefer ; PhD&Dagger ; &Dagger ; &Dagger ; ; Nour Eddine El Mokhtari ; MD&Dagger ; &Dagger ; &Dagger ; ; § ; § ; § ; ; Benjamin A. Goldstein ; PhD¡Î¡Î¡Î ; Mark A. Hlatky ; MD¡Î¡Î¡Î ; Alan S. Go ; MD¶ ; ¶ ; ¶ ; ; Gong-Qing Shen ; MD ; PhD### ; Yan Gong ; PhD???? ; Carl Pepine ; MD???? ; Ross C. Laxton ; BSc? ; John C. Whittaker ; PhD&dagger ; &dagger ; &dagger ; &dagger ; ; W.H. Wilson Tang ; MD ; PhD&dagger ; &dagger ; &dagger ; &dagger ; ; Julie A. Johnson ; PharmD???? ; Qing K. Wang ; PhD ; MBA### ; Themistocles L. Assimes ; MD ; PhD¡Î¡Î¡Î ; Ute Nö ; thlings ; PhD&Dagger ; &Dagger ; &Dagger ; &Dagger ; ; Martin Farrall&dagger ; &dagger ; &dagger ; ; § ; § ; ; § ; § ; ; Hugh Watkins ; MD ; PhD ; FMedSci&dagger ; &dagger ; &dagger ; ; § ; § ; § ; § ; ; A. Mark Richards ; MD ; PhD??? ; Vicky A. Cameron ; PhD??? ; Axel Muendlein ; PhD¶ ; ¶ ; ¶ ; ¶ ; ; Heinz Drexel ; MD¶ ; ¶ ; ¶ ; ¶ ; ; Werner Koch ; PhD## ; Jeong Euy Park ; MD ; PhD¶ ; ¶ ; ; Akinori Kimura ; MD ; PhD¡Î¡Î ; Wei-feng Shen ; PhD#### ; Iain A. Simpson ; MD????? ; Stanley L. Hazen ; MD ; PhD&Dagger ; &Dagger ; &Dagger ; &Dagger ; ; Benjamin D. Horne ; PhD ; MPH&Dagger ; &Dagger ; ; Elizabeth R. Hauser ; PhD&dagger ; &dagger ; ; Arshed A. Quyyumi ; MD&Dagger ; ; Muredach P. Reilly ; MB¶ ; ; Nilesh J. Samani ; MD ; FMedSci¡Î ; Shu Ye ; MD ; PhD? ; s.ye@qmul.ac.uk
- 关键词：9p21 ; angiography ; coronary artery disease ; meta-analysis ; myocardial infarction ; single nucleotide polymorphism
- 刊名：Journal of the American College of Cardiology
- 出版年：2013
- 出版时间：5 March, 2013
- 年：2013
- 卷：61
- 期：9
- 页码：957-970
- 全文大小：2581 K
Objectives
This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD.Background
Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability.
Methods
We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype. Tabular data are provided for each cohort on the presence and burden of angiographic CAD, MI cases with underlying CAD, and the diabetic status of all subjects.
Results
We first confirmed an association between 9p21 and CAD with angiographically defined cases and control subjects (pooled odds ratio [OR]: 1.31, 95 % confidence interval [CI]: 1.20 to 1.43). Among subjects with angiographic CAD (n = 20,987), random-effects model identified an association with multivessel CAD, compared with those with single-vessel disease (OR: 1.10, 95 % CI: 1.04 to 1.17)/copy of risk allele). Genotypic models showed an OR of 1.15, 95 % CI: 1.04 to 1.26 for heterozygous carrier and OR: 1.23, 95 % CI: 1.08 to 1.39 for homozygous carrier. Finally, there was no significant association between 9p21 and prevalent MI when both cases (n = 17,791) and control subjects (n = 15,882) had underlying CAD (OR: 0.99, 95 % CI: 0.95 to 1.03)/risk allele.
Conclusions
The 9p21 locus shows convincing association with greater burden of CAD but not with MI in the presence of underlying CAD. This adds further weight to the hypothesis that 9p21 locus primarily mediates an atherosclerotic phenotype.